Insects as biofactories to produce sphingomyelinase D for Loxosceles antivenom development

MC CALLUM, GREGORIO JUAN; SMITH, IGNACIO; BIRENBAUM, JOAQUÍN MANUEL; RODRIGUEZ, MARÍA SOL; TARGOVNIK, ALEXANDRA MARISA; WOLMAN, FEDERICO JAVIER; DOKMETJIAN, CHRISTIAN; CASCONE, OSVALDO; DE ROODT, ADOLFO; FINGERMANN, MATÍAS; MIRANDA, MARÍA VICTORIA

Congreso; The 2nd International Electronic Conference on Toxins; 2023

Loxosceles species, commonly named “violin” spiders, are widely spread venomousspiders. Clinical cases of Loxosceles bites are more commonly reported in theAmericas, particularly in Argentina, Brazil, Chile and Perú. Most accidents arecharacterized by dermonecrotic lesions, often referred to as necrotic or gangrenousarachnidism. However, in about 10% of the cases a more serious presentation occurs,characterized by a systemic evolution of the pathology that can result in a fataloutcome, mostly in children and elders. Antivenom against Loxosceles species is beingproduced in the Americas since the early 1960s. Its Active Pharmaceutical Ingredientsare immunoglobulins or their fragments obtained from equine plasma of animalshyperimmunized with spiders’ venom. Venom extraction, a very laborious task withvery low yields per spider, is the most relevant production bottleneck. Herein weoptimized a biotechnological process based on Spodoptera frugiperda larvae asbiofactories to obtain a recombinant version from L. laeta sphingomyelinase D(rSmase). The rSmase was recovered high purity level (94.5%) in one-chromatographic step at low cost. Our version of rSmase was able to induce aneutralizing humoral response in horses’ sera. The amount of venom of 17000 spiderscould be replaced with rSmase from 1600 insect larvae. The use of rSmase isexpected to change traditional antivenom production.